摘要:

AbstractHigh‐dose methotrexate (HDMTX, 1,000 mg/m2) and cranial irradiation/sequential chemotherapy (RTSC) were compared for ability to extend complete remission durations in children with acute lymphoblastic leukemia (ALL). Three hundred thirty patients were enrolled in the study, according to our criteria for standard‐risk ALL: a leukocyte count<100 × 109/L, no mediastinal mass, no leukemic involvement of the central nervous system (CNS), and blast cells lacking sheep erythrocyte receptors and surface immunoglobulin. Prednisone‐vin‐cristine‐asparaginase induced complete remissions in 95% of the patients, who were then randomized to receive either HDMTX (n = 154) or RTSC (n = 155). HDMTX was administered with intrathecal MTX for the first 3 weeks following remission induction, and then every 6 weeks with daily mercaptopurine (MP) and weekly oral MTX for a total of 18 months. The RTSC regimen consisted of 1,800 cGy cranial irradiation and intrathecal MTX for 3 weeks, followed by MP/MTX, cyclophosphamide/doxorubicin, and teniposide/cytarabine administered sequentially over 18 months. The final 12 months of treatment for both groups was MP and oral MTX; all patients received intrathecal MTX every 12 weeks.With a median follow‐up of 5 years, complete remission durations have been significantly longer among children treated with HDMTX, compared with RTSC (P= .049) or historical institutional control regimens (P= .002). Approximately 67% of the patients receiving HDMTX and 56% of those receiving RTSC are expected to be in continuous complete remission at 4 years. Overall, isolated CNS relapse rates were similar (P= .17) in the two treatment groups, although by newer risk criteria cranial irradiation could be expected to provide better protection in patients with an unfavorable prognosis. These findings indicate that addition of intermittent HDMTX infusions to conventional chemotherapy is an effective method for extending complete remissions in child

ISSN:0098-1532    

DOI:10.1002/mpo.2950160502

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractOne hundred and twenty‐seven patients with advanced or recurrent squamous cell carcinoma of the head and neck (HNC) were randomized to treatment with methotrexate (MTX) followed 1 hour later by 5‐fluorouracil (5‐FU) (sequence MF), or 5‐fluorouracil followed after 1 hour by methotrexate (sequence FM). One hundred and seventeen patients were evaluable for response. There was no significant difference in response rates between the MF and FM sequences. Overall, 8 patients (6.8%) achieved complete response (CR) and 46 (39.3%) partial response (PR). In 95 previously untreated patients, the overall response rate (CR + PR) was 50%, compared with 31% for previously treated patients (P= 0.02). Survival duration significantly favored the FM sequence in univariate analyses (P= 0.04). Stepwise multivariate Cox model analysis showed that poor performance status (Eastern Cooperative Oncology Group) at study entry (P<0.001) and prior radiotherapy (P= 0.03) were significant adverse predictors for survival. When allowance was made for these factors, a survival difference in favor of the FM sequence remained (P= 0.003). Sequential MTX followed 1 hour later by 5‐FU is not recommended for treatme

ISSN:0098-1532    

DOI:10.1002/mpo.2950160503

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractMeasles and rubella antibody status were determined by ELISA for 115 previously vaccinated children with cancer. Seventy subjects were receiving chemotherapy, and 45 had successfully completed treatment for their malignancy. Overall, 18% of the subjects were seronegative for measles antibody and 8% for rubella antibody. Only 3% of patients lacked both. In general, seronegative individuals were over age 10 years. Subjects born before 1976 were significantly more likely to be seronegative to measles, 29% vs. 11% (P =0.02) and to rubella, 16% vs. 4% (P= 0.03) than those born afterwards. Antibody status showed no apparent relationship to the duration of anticancer therapy. Stored serum samples were available for nine seronegative subjects, of whom five were initially seropositive and then lost antibody during or after the completion of anticancer therapy. Our observations suggest that cancer and its associated therapy interfere with antibody production. In view of the increasing survival rates for childhood cancers, additional studies are needed to assess the immune status of these subjects for all vaccine‐preventable infections. Pending the outcome of further studies, we suggest that long‐term survivors, particularly those born before 1976, or known to be vaccinated at less than 13 months of age, be tested after the completion of therapy for antibody to measles and rubella (and mumps). Also, immune serum globulin should be considered for any previously immunized patient with a close exposure to an active case of meas

ISSN:0098-1532    

DOI:10.1002/mpo.2950160504

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractOne hundred twenty‐two patients with advanced adenocarcinoma of the breast were randomized to receive adriamycin (AD) alone or a combination of VP‐16 plus lower dose adriamycin (VAD). The patients were stratified to good and poor risk. The starting dose (day 1) of AD was 60 mg/m2for good risk and 45 mg/m2for poor risk. The starting dose of the VAD combination for the good‐risk patient was VP‐16, 75 mg/m2daily × 5 plus adriamycin 35 mg/m2.The poor‐risk dose for VAD was VP‐16, 50 mg/m2daily × 5 plus adriamycin, 30 mg/m2on day 1. The total dose of AD was 450 mg/m2on both arms. The patients who were on the VAD arm continued on VP‐16 maintenance. Both arms were repeated every 21 days. There were 54 evaluable patients on the adriamycinarm and 52 evaluable patients on the VAD arm. Both arms were similar with regard to age, menopausal status, performance status, and prior hormonal therapy. More hematologic toxicity was seen in the adriamycin arm. Complete responses were observed on both arms, three (5%) with adriamycin and three (5%) with combination. Eleven (19%) and ten (18%) partial responses were observed with the adriamycin and VP‐16 plus adriamycin, respectively. AD produced more stable disease than VAD (41% vs. 29%). Complete responses were seen only in the good‐risk patients. Time to progression was delayed on the combination arm (P= 0.02). The survival in both arms was similar. The addition of VP‐16 to adriamycin does not offer an importa

ISSN:0098-1532    

DOI:10.1002/mpo.2950160505

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractIn a retrospective cohort study, the level of education attained by 2,283 long‐term survivors of childhood and adolescent cancer was investigated and compared with that of 3,270 sibling controls. Survivors of central nervous system tumors were significantly less likely than controls to complete eight grades of school or, if they completed high school, to enter college. No significant differences in educational achievement were found for survivors of non‐central nervous system cancers. The educational deficit of survivors of brain tumors was especially striking for tumors of the ventricles or cerebral hemispheres, and the deficit was more severe for those treated with radiation therapy than by surgery alone. Early age at diagnosis of a central nervous system tumor was associated with a larger educational deficit than late age at diagnosis. These findings are reassuring for the majority of long‐term survivors of childhood and adolescent cancers given therapies used prior to

ISSN:0098-1532    

DOI:10.1002/mpo.2950160506

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

Abstract2‐Deoxycoformycin (DCF) was added to an intensive Pediatric Oncology Group protocol ( 8303) for children with T‐cell acute lymphoblastic leukemia or T‐cell lymphoblastic lymphoma in first relapse. Twenty‐seven patients received one or more courses of DCF at 15 mg/m2/day as a 3‐day continuous infusion immediately after achieving a second remission with a four‐drug reinduction regimen. Renal and neuromuscular toxicities were frequent and occasionally severe despite the provision of a source of adenosine deaminase by means of a packed red cell transfusion 1 day following the infusion of DCF. Hepatic toxicity, manifested by transaminase elevations, accompanied 62% of the courses. The median duration of the second complete re mission was 4 months (range 2‐16+ months) with only two of the 27 patients still in remission at 13 + and 16 + months. Plasma concentrations of deoxyadenosine (dAdo) and the ratio of red cell deoxyadenosine triphosphate to adenosine triphosphate (dATP:ATP) were measured prior to the DCF infusion and on day 4. A dATP:ATP ratio of 1.0 or greater was seen in two patients with acute renal failure. There was no apparent correlation between toxicity or response and the plasma dAdo concentrations. DCF administered according to this dose and schedule was excessively toxic and did not appreciably prolong the duration of the second complete remission in children with T‐cell lymphoblast

ISSN:0098-1532    

DOI:10.1002/mpo.2950160507

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractA phase I/II study of bisantrene using a 3‐week schedule was undertaken in 171 children with refractory leukemias and solid tumors. The doses ranged from 190 to 430 mg/m2. The maximum tolerated dose for children with solid tumors and acute leukemias was 280 mg/m2and 360 mg/m2every 3 weeks, respectively. The dose limiting toxicities were hepatic and hematologic. One patient with ALL achieved a complete remission and partial responses were observed in three patients with soft‐tissue sarcomas. The data indicate that bisantrene, at the doses and schedule used in this study, has limited antitumor activity in pretreated children with Can

ISSN:0098-1532    

DOI:10.1002/mpo.2950160508

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractMetaiodobenzylguanidine (MIBG) has been used for the detection and treatment of neuroectodermal tumors, including neuroblastoma. We report our experience with131I‐MIBG used diagnostically in neuroblastoma patients with relapse. Thirty‐eight studies were performed in 26 patients. There were 24 children (range 3 months‐14 years) and two adults. While the study was found to be both sensitive and specific for the presence of disease, there are instances of discordance. False‐negative studies were found with a markedly anaplastic tumor and with two mature ganglioneuromas. A bone lesion was negative with131I‐MIBG, but positive on bone scan. A biopsy confirmed the presence of neuroblastoma. Caution should be exercised when scanning pretreated patients, and perhaps with newly diagnosed patient

ISSN:0098-1532    

DOI:10.1002/mpo.2950160509

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

ISSN:0098-1532    

DOI:10.1002/mpo.2950160510

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractTo improve on drug dosage decisions, the method of “marginal analysis,” traditionally found in the economics literature, is applied to the dose‐response curve. Marginal analysis is first defined and explained, next the technique is redefined for the clinical setting of dose determination subject to drug efficacy and side effects, and finally an example using adjuvant adriamycin chemotherapy in osteo sarcoma is presented. By not using “marginal analysis,” clinicians may not be maximizing overall therapeutic success or patient survival. Implications for future clinical trials are discussed, and a suggestion for estimating dose‐response is proposed. The technique described should be readily applicable to many dosing problems, and need not be restricted to chemotherapy dosin

ISSN:0098-1532    

DOI:10.1002/mpo.2950160511

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY